Effects of pesticides and toxic substances on behavioral and morphological reproductive development: endocrine versus nonendocrine mechanisms.
Exposure to toxic substances or pesticides during critical perinatal developmental periods can alter reproductive and central nervous system (CNS) function in a manner that does not compromise the growth and viability of the fetus but causes functional alterations that become apparent later in life. While some "CNS/behavioral teratogens" are mutagenic or alter cell division, other chemicals produce alterations of CNS development via endocrine-mediated mechanisms. The following discussion will focus on studies conducted primarily in our laboratory that describe how pesticides and toxic substances alter development of the reproductive and central nervous systems as a consequence of organizational or activational exposures. Abnormal behavior and morphology can result from exposure to endocrine-disrupting toxicants by altering organization of the CNS during critical stages of life or activation of behavior after puberty. Some of the toxicants that alter rodent sexual differentiation include xenoestrogens, antiandrogenic pesticides, and dioxin-like toxic substances. Chemicals that alter sex-linked nonreproductive and reproductive CNS development via nonhormonal mechanisms are also discussed in order to demonstrate that multiple mechanisms of action are involved in the development of behavioral abnormalities in pre- and perinatally exposed offspring. The fact that reproductive function (behavioral, biochemical, and morphological) can be altered via such a wide variety of mechanisms indicates that hazard identification in this area cannot rely solely on the detection of endocrine activity.
Gray
L E
LE
Endocrinology Branch, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. gray@herl45.herl.epa.gov
Ostby
J
J
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000254:growth & development; D004781:Environmental Exposure; D005260:Female; D005506:Food Contamination; D005835:Genitalia / Q000187:drug effects / Q000254:growth & development; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000254:growth & development; D010575:Pesticides / Q000494:pharmacology / Q000633:toxicity*; D011627:Puberty / Q000187:drug effects; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D012725:Sexual Behavior / Q000187:drug effects
D012739:Gonadal Steroid Hormones; D010575:Pesticides